2-(1-chloropropyl)-8-trifluoromethyl-4H-3,1-benzoxazine-4-one | 114351-20-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 2-(1-chloropropyl)-8-trifluoromethyl-4H-3,1-benzoxazine-4-one
• 英文别名: 4H-3,1-Benzoxazin-4-one, 2-(1-chloropropyl)-8-(trifluoromethyl)-；2-(1-chloropropyl)-8-(trifluoromethyl)-3,1-benzoxazin-4-one
• CAS: 114351-20-1
• 化学式: C₁₂H₉ClF₃NO₂
• 分子量: 291.657
• InChiKey: FCZXFTQRMCBGLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(1-chloropropyl)-8-trifluoromethyl-4H-3,1-benzoxazine-4-one 在 盐酸 、 4-二甲氨基吡啶 、 正丁基锂 、 水 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 19.58h， 生成 1-[4-oxo-3-(1,3-thiazol-2-ylcarbamoyl)-8-(trifluoromethyl)-1H-quinolin-2-yl]propyl dodecanoate
  参考文献：
  名称：

  具有抗关节炎和止痛作用的4-羟基-3-喹啉甲酰胺。

  摘要：

  已经合成了一系列的4-羟基-3-喹啉甲酰胺，并通过口服途径评价了角叉菜胶引起的足部水肿和佐剂引起的关节炎中的抗炎药，以及乙酸引起的扭体试验中的镇痛药。在最活跃的分子中，有些已经显示出止痛和急性抗炎活性。其他化合物，例如化合物24、37和52，仅是有效的外周镇痛药。活性为1 mg / kg（ED50）的化合物52是该系列中最有效的化合物。一些在2位上被醇，酯或胺官能团取代的类似物显示出与吡罗昔康相同的有效抗关节炎活性，并且在炎症和伤害感受的急性试验中也具有活性。他们抑制了微摩尔浓度的环氧合酶和5-脂氧合酶的活性。化合物102（RU 43526）显示出有效的抗关节炎活性（佐剂诱发的关节炎，ED50 = 0.7 mg / kg，口服）和胃肠道耐受性（ED100大于250 mg / kg，口服），因此，目前正在接受广泛的药理评估。

  DOI：

  10.1021/jm00402a034
• 作为产物：
  描述：

  2-氨基-3-(三氟甲基)苯甲酸 、 2-氯丁酰氯 在 N-甲基吗啉 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以97%的产率得到2-(1-chloropropyl)-8-trifluoromethyl-4H-3,1-benzoxazine-4-one
  参考文献：
  名称：

  具有抗关节炎和止痛作用的4-羟基-3-喹啉甲酰胺。

  摘要：

  已经合成了一系列的4-羟基-3-喹啉甲酰胺，并通过口服途径评价了角叉菜胶引起的足部水肿和佐剂引起的关节炎中的抗炎药，以及乙酸引起的扭体试验中的镇痛药。在最活跃的分子中，有些已经显示出止痛和急性抗炎活性。其他化合物，例如化合物24、37和52，仅是有效的外周镇痛药。活性为1 mg / kg（ED50）的化合物52是该系列中最有效的化合物。一些在2位上被醇，酯或胺官能团取代的类似物显示出与吡罗昔康相同的有效抗关节炎活性，并且在炎症和伤害感受的急性试验中也具有活性。他们抑制了微摩尔浓度的环氧合酶和5-脂氧合酶的活性。化合物102（RU 43526）显示出有效的抗关节炎活性（佐剂诱发的关节炎，ED50 = 0.7 mg / kg，口服）和胃肠道耐受性（ED100大于250 mg / kg，口服），因此，目前正在接受广泛的药理评估。

  DOI：

  10.1021/jm00402a034

文献信息

• Certain 1,3-dihydro-1-[heterocyclic)imino]-furo-[3,4-b]quinoline 9-ol
  申请人：Roussel Uclaf

  公开号：US04736033A1

  公开（公告）日：1988-04-05

  A 4-hydroxy-3-quinoline-carboxamides of the formula ##STR1## wherein X is in the 5,6,7 or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CH.sub.3, --OCF.sub.3 or --SCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of a heterocycle connected to the nitrogen by a carbon atom selected from thiazolyl, 4,5-dihydro-thiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidinyl or tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms or phenyl optionally substituted with at least one member of the group consisting of --OH, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CH.sub.3, --NO.sub.2 or halogen, R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms or aryl, R.sub.4 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms or aryl, and their non-toxic, pharmaceutically acceptable acid addition salts and salts with non-toxic, pharmaceutically acceptable bases having very good analgesis activity and a non-negligible anti-inflammatory activity and novel intermediates.

  式##STR1##中的4-羟基-3-喹啉羧酰胺，其中X位于5、6、7或8位，并选自由氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、--CH.sub.3、--OCF.sub.3或--SCF.sub.3的群，R.sub.1选自由氢和1至4个碳原子的烷基的群，R.sub.2选自由氮原子连接的杂环，所述杂环由噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基或四唑基中的碳原子选自，所有这些基可选择地用1至4个碳原子的烷基或苯基取代，所述苯基可选择地用--OH、1至4个碳原子的烷基、1至4个碳原子的烷氧基、--CH.sub.3、--NO.sub.2或卤素中的至少一种成员取代，R.sub.3选自由氢、1至4个碳原子的烷基或芳基的群，R.sub.4选自由氢、1至4个碳原子的烷基或芳基的群，以及它们的无毒、药学上可接受的酸盐和与非毒性、药学上可接受的碱形成的盐，具有非常好的镇痛活性和非可忽略的抗炎活性和新颖的中间体。
• 4-Hydroxy-3-quinoline-carboxylic acid derivatives
  申请人：Roussel Uclaf

  公开号：US04486438A1

  公开（公告）日：1984-12-04

  Novel 4-hydroxy-3-quinoline-carboxamides of the formula ##STR1## wherein X is in the 5,6,7 or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --OCF.sub.3 and --SCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of thiazolyl, 4,5-dihydro-thiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidinyl and tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl optionally substituted with at least one member of the group consisting of --OH, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.4 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and ##STR2## R.sub.5 ' is selected from the group consisting of alkyl of 1 to 4 carbon atoms and aryl and their non-toxic, pharmaceutically acceptable acid addition salts and salts with non-toxic, pharmaceutically acceptable bases having very good analgesic activity and a non-negligible anti-inflammatory activity and novel intermediates.

  新型4-羟基-3-喹啉羧酰胺的化学式为##STR1##其中X位于5,6,7或8位，并选自由氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--OCF.sub.3和--SCF.sub.3组成的群，R.sub.1选自由氢和1至4个碳原子的烷基组成的群，R.sub.2选自噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基和四唑基组成的群，所有这些基可选择地用1至4个碳原子的烷基和苯基替代，所述苯基可选择地用--OH、1至4个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--NO.sub.2和卤素中的至少一种成员替代，R.sub.3选自由氢、1至4个碳原子的烷基和芳基组成的群，R.sub.4选自由氢、1至4个碳原子的烷基和芳基组成的群，R.sub.5选自由氢、1至4个碳原子的烷基和##STR2##R.sub.5'选自由1至4个碳原子的烷基和芳基组成的群，以及它们的无毒、药学上可接受的酸盐和与无毒、药学上可接受的碱盐具有非常好的镇痛活性和不可忽视的抗炎活性的盐和新型中间体。
• Novel 4-hydroxy-3-quinoline-carboxylates having analgesic and
  申请人：Roussel Uclaf

  公开号：US04735951A1

  公开（公告）日：1988-04-05

  Novel optical isomers and racemates of 4-hydroxy-3-quinoline-carboxylates of the formula ##STR1## wherein X is in the 5-, 6-, 7- or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --SCF.sub.3 and --OCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl and tetrazolyl all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl substituted with at least one member of the group consisting of --OH, alkyl and alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen, R.sub.3 and R.sub.4 are individually selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5 is selected from the group consisting of aryl of 6 to 14 carbon atoms, heteroaryl of 3 to 14 carbon atoms, alkyl of 1 to 14 carbon atoms, alkyl substituted with --NH.sub.2, --NHAlk or ##STR2## alkenyl of 2 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms substituted with aryl of 6 to 14 carbon atoms, Alk and Alk' are alkyl of 1 to 6 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts with the proviso that when X is 8-CF.sub.3, R.sub.1 and R.sub.3 are hydrogen, R.sub.2 is 2-thiazolyl, R.sub.4 is methyl, R.sub.5 is not methyl having analgesic and anti-inflammatory activity.

  4-羟基-3-喹啉羧酸酯的新型光学异构体和外消旋体，其化学式为##STR1## 其中，X位于5-、6-、7-或8-位，选择自氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--SCF.sub.3和--OCF.sub.3的群体中，R.sub.1选择自氢和1至4个碳原子的烷基，R.sub.2选择自噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基和四唑基，其中所有基团都可以被1至4个碳原子的烷基和苯基取代，苯基被至少一种来自--OH、1至4个碳原子的烷基和烷氧基、--CF.sub.3、--NO.sub.2和卤素的基团取代，R.sub.3和R.sub.4各自选择自氢、1至4个碳原子的烷基和芳基，R.sub.5选择自6至14个碳原子的芳基、3至14个碳原子的杂环芳基、1至14个碳原子的烷基、被--NH.sub.2、--NHAlk或##STR2## 取代的烷基、2至6个碳原子的烯基、被6至14个碳原子的芳基取代的2至6个碳原子的烯基，Alk和Alk'是1至6个碳原子的烷基，以及其非毒性、药学上可接受的酸盐，但当X为8-CF.sub.3时，R.sub.1和R.sub.3为氢，R.sub.2为2-噻唑基，R.sub.4为甲基，R.sub.5不为甲基，具有镇痛和抗炎活性。
• 4-OH-quinoline carboxylic acid amides having analgesic and
  申请人：Roussel Uclaf

  公开号：US04845105A1

  公开（公告）日：1989-07-04

  A compound selected from the group consisting of optical isomers and racemates of 4-hydroxy-3-quinoline carboxylates of the formula ##STR1## wherein X is in the 5-, 6-, 7- or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --SCF.sub.3 and --OCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl and tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl and phenyl substituted with at least one member of the group consisting of --OH, alkyl and alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen, A is either ##STR2## in which R.sub.3 and R.sub.4 are individually selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5 is selected from the group consisting of aryl of 6 to 14 carbon atoms, heteroaryl of 3 to 14 carbon atoms, alkyl of 1 to 14 carbon atoms, alkyl substituted with --NH.sub.2, --NHAlk or ##STR3## alkenyl of 2 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms substituted with aryl of 6 to 14 carbon atoms, Alk and Alk' are alkyl of 1 to 6 carbon atoms or, when R.sub.1 is hydrogen, A is ##STR4## and R.sub.3a are individually selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, aryl and ##STR5## or R.sub.2a and R.sub.3a together form acetonide, R.sub.4a is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5a is selected from the group consisting of alkyl of 1 to 4 carbon atoms and aryl with the proviso that when X is 8--CF.sub.3, R.sub.1 and R.sub.3 are hydrogen, R.sub.2 is 2-thiazolyl, R.sub.4 is methyl, R.sub.5 is not methyl and their non-toxic, pharmaceutically acceptable salts with acids or bases having analgesic and anti-inflammatory activity.

  从由式##STR1##中4-羟基-3-喹啉羧酸盐的光学异构体和外消旋体组成的群体中选择的化合物，其中X位于5-、6-、7-或8-位置，选择自氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--SCF.sub.3和--OCF.sub.3的群体中，R.sub.1选择自氢和1至4个碳原子的烷基，R.sub.2选择自噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基和四唑基，所有这些基都可以选择性地用1至4个碳原子的烷基和苯基以及苯基上至少一个成员的取代物，所述成员选择自--OH、1至4个碳原子的烷基和烷氧基、--CF.sub.3、--NO.sub.2和卤素，A可以是##STR2##其中R.sub.3和R.sub.4分别选择自氢、1至4个碳原子的烷基和芳基，R.sub.5选择自6至14个碳原子的芳基、3至14个碳原子的杂芳基、1至14个碳原子的烷基、用--NH.sub.2、--NHAlk或##STR3##取代的烷基、2至6个碳原子的烯基、用6至14个碳原子的芳基取代的2至6个碳原子的烯基，Alk和Alk'是1至6个碳原子的烷基，或者当R.sub.1为氢时，A为##STR4##R.sub.3a选择自氢、1至4个碳原子的烷基、芳基和##STR5##或R.sub.2a和R.sub.3a一起形成缩醛，R.sub.4a选择自氢、1至4个碳原子的烷基和芳基，R.sub.5a选择自1至4个碳原子的烷基和芳基，但当X为8--CF.sub.3时，R.sub.1和R.sub.3为氢，R.sub.2为2-噻唑基，R.sub.4为甲基，R.sub.5不为甲基，以及它们与酸或碱的非毒性、药学上可接受的盐，具有镇痛和抗炎活性。
• Preparation of amides of 4-hydroxy-3-quinoline-carboxylic acid
  申请人：Roussel Uclaf

  公开号：US04596875A1

  公开（公告）日：1986-06-24

  Novel 4-hydroxy-3-quinoline-carboxamides of the formula ##STR1## wherein X is in the 5,6,7 or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --OCF.sub.3 and --SCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of thiazolyl, 4,5-dihydro-thiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidinyl and tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl optionally substituted with at least one member of the group consisting of --OH, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen, R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.4 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and ##STR2## R.sub.5 ' is selected from the group consisting of alkyl of 1 to 4 carbon atoms and aryl and their non-toxic, pharmaceutically acceptable acid addition salts and salts with non-toxic, pharmaceutically acceptable bases having very good analgesic activity and a non-negligible anti-inflammatory activity and novel intermediates.

  化合物的名称为4-羟基-3-喹啉甲酰胺，化学式如下：##STR1## 其中X位于5、6、7或8位，选自氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--OCF.sub.3和--SCF.sub.3的群组，R.sub.1选自氢和1至4个碳原子的烷基，R.sub.2选自噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基和四唑基，均可选用1至4个碳原子的烷基和苯基，后者可选择至少一种取代基，所述取代基选自--OH、1至4个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--NO.sub.2和卤素的群组，R.sub.3选自氢、1至4个碳原子的烷基和芳基，R.sub.4选自氢、1至4个碳原子的烷基和芳基，R.sub.5选自氢、1至4个碳原子的烷基和##STR2##，R.sub.5'选自1至4个碳原子的烷基和芳基。该化合物及其中间体具有很好的镇痛活性和非常重要的抗炎活性，以及其非毒性、药学上可接受的酸盐和非毒性、药学上可接受的碱盐。